Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients

We investigated whether urinary vascular non-inflammatory molecule-1 (vanin-1), a promising early-onset tubular injury marker, correlates with other established tubular injury markers and is associated with graft failure in kidney transplant recipients (KTR). We measured 24 h urinary vanin-1 excretion in 656 KTR (age 53 ± 13 years, 43% female, estimated glomerular filtration rate (eGFR) 53 ± 21 mL/min/1.73 m2) who had undergone kidney transplantation ≥ 1 year. The median 24 h urinary vanin-1 excretion was 145 [51–331] pmol/24 h. 24 h urinary vanin-1 excretion correlated weakly but significantly with other tubular injury markers (ρ = 0.14, p < 0.001 with urinary liver-type fatty acid binding protein, ρ = 0.13, p = 0.001 with urinary post-translationally modified fetuin-A protein, and ρ = 0.10, p = 0.011 with plasma neutrophil gelatinase-associated lipocalin) and with eGFR (ρ = − 0.13, p = 0.001). During a median follow-up of 7.4 [4.9–8.0] years, 94 (14%) KTR developed death-censored graft failure. In multivariable Cox regression analyses, 24 h urinary vanin-1 excretion was not associated with an increased risk of death-censored graft failure (adjusted hazard ratio [95% confidence interval] = 0.96 [0.86–1.07], p = 0.5). In conclusion, our findings do not support the role of urinary vanin-1 as a biomarker of graft failure after kidney transplantation.

Page Supplementary Table 2. Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which urinary vanin-1 below the detection limit was excluded.
Page Supplementary Table 3. Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which 24h urinary vanin-1 excretion outside the 2.5 th -97.5 th percentile was excluded.
Page Supplementary Table 4. Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which 24h urinary vanin-1 excretion outside the 5 th -95 th percentile was excluded.Of 656 kidney transplant recipients, 14 of them had urinary vanin-1 below the detection limit, leaving 642 kidney transplant recipients for Cox proportional-hazard regression analyses.Death-censored graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis.

Supplementary
Model 1 was adjusted for age, sex, and body surface area.Model 2 was further adjusted for the estimated glomerular filtration rate based on the creatinine-based CKD-EPI formula.Model 3 was further adjusted for 24-hour urinary protein excretion.Model 4 was further adjusted for the use of proliferation inhibitors.95% CI, 95% confidence interval; HR, hazard ratio.3. Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which 24h urinary vanin-1 excretion outside the 2.5 th -97.5 th percentile were excluded..5Of 656 kidney transplant recipients, 33 of them had urinary vanin-1 below the 5 th percentile, and another 33 had urinary vanin-1 above the 95 th percentile, leaving 590 kidney transplant recipients for Cox proportional-hazard regression analyses.Death-censored graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis.Model 1 was adjusted for age, sex, and body surface area.Model 2 was further adjusted for the estimated glomerular filtration rate based on the creatinine-based CKD-EPI formula.Model 3 was further adjusted for 24-hour urinary protein excretion.Model 4 was further adjusted for the use of proliferation inhibitors.95% CI, 95% confidence interval; HR, hazard ratio.

Urinary Vanin-1, Tubular Injury, and Graft Failure in Kidney Transplant Recipients SUPPLEMENTAL MATERIAL Table of contents Supplementary Figure 1.
Flow chart of the study population selection Page Supplementary

Table 1 .
STROBE Statement -Checklist of items that should be included in reports of cohort studies.

Table 5 .
Cox proportional-hazard regression analysis of the associations of urinary vanin-1 excretion with graft failure using various transformations in adjusted Cox regression models.Page Supplementary

Table 6 .
Prospective analysis of the association of urinary Vanin-

Table 2 .
Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which

Table 4 .
Of 656 kidney transplant recipients, 17 of them had urinary vanin-1 below the 2.5 th percentile, and another 17 had urinary vanin-1 above the 97.5 th percentile, leaving 622 kidney transplant recipients for Cox proportional-hazard regression analyses.Death-censored graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis.Model 1 was adjusted for age, sex, and body surface area.Model 2 was further adjusted for the estimated glomerular filtration rate based on the creatinine-based CKD-EPI formula.Model 3 was further adjusted for 24-hour urinary protein excretion.Model 4 was further adjusted for the use of proliferation inhibitors.95% CI, 95% confidence interval; HR, hazard ratio.Prospective analysis of the association of 24h urinary vanin-1 excretion with death-censored graft failure in which 24h urinary vanin-1 excretion outside the 5 th -95 th percentile were excluded.